Evidence map›Paper›PMID 25599332›Full record

ArticleCirculation research2015

Canonical wnt signaling regulates atrioventricular junction programming and electrophysiological properties.

Benjamin S Gillers, Aditi Chiplunkar, Haytham Aly, Tomas Valenta, Konrad Basler, Vincent M Christoffels, Igor R Efimov, Bastiaan J Boukens, Stacey Rentschler

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In one paragraph

Article in Circulation research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

59 citing papers in PubMed, 100 citations in OpenAlex.

  1. Trial
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  13. Development of the Cardiac Conduction System.Advances in experimental medicine and biology · 2024
    Article
  14. Review
  15. Cells · 2023
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  16. The role of β-catenin in cardiac diseases.Frontiers in pharmacology · 2023
    Review
  17. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Benjamin S GillersFrom the Department of Medicine, Cardiovascular Division (B.S.G., A.C., H.A., S.R.), and Department of Developmental Biology (B.S.G., A.C., H.A., S.R.), Washington University School of Medicine, St. Louis, MO; Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland (T.V., K.B.); Department of Anatomy, Embryology, and Physiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (V.M.C.); and Department of Biomedical Engineering, Washington University, St. Louis, MO (I.R.E., B.J.B., S.R.).
Aditi ChiplunkarFrom the Department of Medicine, Cardiovascular Division (B.S.G., A.C., H.A., S.R.), and Department of Developmental Biology (B.S.G., A.C., H.A., S.R.), Washington University School of Medicine, St. Louis, MO; Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland (T.V., K.B.); Department of Anatomy, Embryology, and Physiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (V.M.C.); and Department of Biomedical Engineering, Washington University, St. Louis, MO (I.R.E., B.J.B., S.R.).
Haytham AlyFrom the Department of Medicine, Cardiovascular Division (B.S.G., A.C., H.A., S.R.), and Department of Developmental Biology (B.S.G., A.C., H.A., S.R.), Washington University School of Medicine, St. Louis, MO; Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland (T.V., K.B.); Department of Anatomy, Embryology, and Physiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (V.M.C.); and Department of Biomedical Engineering, Washington University, St. Louis, MO (I.R.E., B.J.B., S.R.).
Tomas ValentaFrom the Department of Medicine, Cardiovascular Division (B.S.G., A.C., H.A., S.R.), and Department of Developmental Biology (B.S.G., A.C., H.A., S.R.), Washington University School of Medicine, St. Louis, MO; Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland (T.V., K.B.); Department of Anatomy, Embryology, and Physiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (V.M.C.); and Department of Biomedical Engineering, Washington University, St. Louis, MO (I.R.E., B.J.B., S.R.).
Konrad BaslerFrom the Department of Medicine, Cardiovascular Division (B.S.G., A.C., H.A., S.R.), and Department of Developmental Biology (B.S.G., A.C., H.A., S.R.), Washington University School of Medicine, St. Louis, MO; Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland (T.V., K.B.); Department of Anatomy, Embryology, and Physiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (V.M.C.); and Department of Biomedical Engineering, Washington University, St. Louis, MO (I.R.E., B.J.B., S.R.).
Vincent M ChristoffelsFrom the Department of Medicine, Cardiovascular Division (B.S.G., A.C., H.A., S.R.), and Department of Developmental Biology (B.S.G., A.C., H.A., S.R.), Washington University School of Medicine, St. Louis, MO; Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland (T.V., K.B.); Department of Anatomy, Embryology, and Physiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (V.M.C.); and Department of Biomedical Engineering, Washington University, St. Louis, MO (I.R.E., B.J.B., S.R.).
Igor R EfimovFrom the Department of Medicine, Cardiovascular Division (B.S.G., A.C., H.A., S.R.), and Department of Developmental Biology (B.S.G., A.C., H.A., S.R.), Washington University School of Medicine, St. Louis, MO; Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland (T.V., K.B.); Department of Anatomy, Embryology, and Physiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (V.M.C.); and Department of Biomedical Engineering, Washington University, St. Louis, MO (I.R.E., B.J.B., S.R.).
Bastiaan J BoukensFrom the Department of Medicine, Cardiovascular Division (B.S.G., A.C., H.A., S.R.), and Department of Developmental Biology (B.S.G., A.C., H.A., S.R.), Washington University School of Medicine, St. Louis, MO; Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland (T.V., K.B.); Department of Anatomy, Embryology, and Physiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (V.M.C.); and Department of Biomedical Engineering, Washington University, St. Louis, MO (I.R.E., B.J.B., S.R.).
Stacey RentschlerFrom the Department of Medicine, Cardiovascular Division (B.S.G., A.C., H.A., S.R.), and Department of Developmental Biology (B.S.G., A.C., H.A., S.R.), Washington University School of Medicine, St. Louis, MO; Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland (T.V., K.B.); Department of Anatomy, Embryology, and Physiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (V.M.C.); and Department of Biomedical Engineering, Washington University, St. Louis, MO (I.R.E., B.J.B., S.R.). Stacey.rentschler@wustl.edu.
University of Zurich · CHUniversity of Amsterdam · NLAcademic Medical Center · NL

Funding

Expansion of cardiac and hematopoietic progenitors by Wnt and NotchU01HL100405 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI EPSTEIN, JONATHAN A., MORRISEY, EDWARD E · 2009 to 2015
$8.1M
CELL BIOLOGIC APPROACHES TO DIABETES RESEARCHT32DK007296 · NIDDK · WASHINGTON UNIVERSITY · PI COLONNA, MARCO · 1986 to 2014
$3.3M
The Role of Notch Signaling in ArrhythmogenesisK08HL107449 · NHLBI · WASHINGTON UNIVERSITY · PI RENTSCHLER, STACEY LYNN · 2011 to 2015
$660k
NHLBI NIH HHS K08 HL107449NHLBI NIH HHS U01 HL100405NIDDK NIH HHS 5T32DK007296NIDDK NIH HHS T32 DK007296
6 · The paper itself

Abstract

rationaleProper patterning of the atrioventricular canal (AVC) is essential for delay of electrical impulses between atria and ventricles, and defects in AVC maturation can result in congenital heart disease.

objectiveTo determine the role of canonical Wnt signaling in the myocardium during AVC development. METHODS AND

resultsWe used a novel allele of β-catenin that preserves β-catenin's cell adhesive functions but disrupts canonical Wnt signaling, allowing us to probe the effects of Wnt loss of function independently. We show that the loss of canonical Wnt signaling in the myocardium results in tricuspid atresia with hypoplastic right ventricle associated with the loss of AVC myocardium. In contrast, ectopic activation of Wnt signaling was sufficient to induce formation of ectopic AV junction-like tissue as assessed by morphology, gene expression, and electrophysiological criteria. Aberrant AVC development can lead to ventricular pre-excitation, a characteristic feature of Wolff-Parkinson-White syndrome. We demonstrate that postnatal activation of Notch signaling downregulates canonical Wnt targets within the AV junction. Stabilization of β-catenin protein levels can rescue Notch-mediated ventricular pre-excitation and dysregulated ion channel gene expression.

conclusionsOur data demonstrate that myocardial canonical Wnt signaling is an important regulator of AVC maturation and electric programming upstream of Tbx3. Our data further suggest that ventricular pre-excitation may require both morphological patterning defects, as well as myocardial lineage reprogramming, to allow robust conduction across accessory pathway tissue.

Indexed as

Wnt Signaling PathwayAnimalsbeta CateninHeart AtriaHeart Conduction SystemHeart VentriclesMiceMyocardiumReceptors, NotchT-Box Domain ProteinsTricuspid Atresiabeta CateninCTNNB1 protein, mouseReceptors, NotchT-Box Domain ProteinsTbx3 protein, mousearrhythmias, cardiacarrhythmogenic cardiomyopathyNotch signaling pathwayseptal defectstricuspid atresiaventricular pre-excitationWnt signaling pathway

Identifiers

PMID25599332
PMCPMC4312529
OpenAlexW2106587421

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.